Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients.

A Randomised, Double-blind, 5 Treatment Arms, 4-period, Incomplete Cross-over Study to Determine the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (FDC) (2.5 / 5 µg; and 5 / 5 µg) (Delivered by the Respimat® Inhaler) Compared With Tiotropium (5 µg), Olodaterol (5 µg ) and Placebo (Delivered by the Respimat® Inhaler) on Lung Hyperinflation and Exercise Endurance Time During Constant Work Rate Cycle Ergometry in Patients With Chronic Obstructive Pulmonary Disease (COPD) [MORACTO TM 2]

The primary objective of this trial is to investigate the effect of 6 weeks treatment with tiotropium + olodaterol fixed dose combination inhalation solution on lung hyperinflation and exercise tolerance in patients with COPD.

Inclusion criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.

2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

   Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 <80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1.

3. Male or female patients, between 40 and 75 years of age (inclusive) on day of signing informed consent.

4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years.

Exclusion criteria:

1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study

2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT >x2 ULN, SGPT >x2 ULN, bilirubin >x2 ULN or creatinine >x2 ULN will be excluded regardless of clinical condition

3. Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.

   Patients with any of the following conditions:

4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists)

5. A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class side effect profile of ß2-agonists)

6. A history of myocardial infarction within 1 year of screening visit (Visit 1)

7. Unstable or life-threatening cardiac arrhythmia

8. Hospitalized for heart failure within the past year

9. Known active tuberculosis

10. A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed)

11. A history of life-threatening pulmonary obstruction

12. A history of cystic fibrosis

13. Clinically evident bronchiectasis

14. A history of significant alcohol or drug abuse

15. Any contraindications for exercise testing.

16. Patients who have undergone thoracotomy with pulmonary resection (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1)

17. Patients being treated with any oral ß-adrenergics

18. Patients being treated with oral corticosteroid medication at unstable doses

19. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits

20. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program

21. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.

22. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit

23. Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, BAC, EDTA or any other component of the Respimat® inhalation solution delivery system

24. Pregnant or nursing women

25. Women of childbearing potential not using highly effective methods of birth control.